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There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression.

The development of methods based on the “multivantaged” assessment of behavioral, affect, and cognitive constructs in patients with affective disorders, is reponed. The state and outcome constructs were derived for application in clinical and psychobiological studies, particularly those aimed at testing biobehavioral hypotheses and the evaluation of the effects of drugs. The development of the constructs is based on the combining of scales from established measures which assess the patient in the interview, on the ward, from his self-report, and from a new vantage, through video methodology. Psychometric analyses primarily from data from the NIMH Collaborative Study of the Psychobiology of Depression describe the assembling of the 11 state constructs, and the estimation of their reliabilities, their interrelationships, and their validities. The methods are shown to be capable of characterizing pathologic and “normal” affects, social and expressive behaviors, and impairments in the cognitive and somatic spheres. They differentiated such diverse groups as depressives, manics, and normals, and such behaviorally similar depressive types as the unipolar and bipolar. Preliminary evidence is reported which indicates differential sensitivity to the effects of tricyclic drugs

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